PD26-12: HIVEC-E: Spanish multicenter Prospective experience with recirculant hyperthermic MMC with Combat BRS HIVEC system

Ana Plata Bello*, La Laguna-Santa Cruz de Tenerife, Spain, Felix Guerrero-Ramos, Madrid, Spain, Carlos García, La Laguna-Santa Cruz de Tenerife, Spain, Alejandro González Diaz, Ignacio González-Valcárcel, Jose Manuel De la Morena-Gallego, Francisco Javier Diaz Goizueta, Madrid, Spain, Julio Fernández-Alamo, Torrejon de Ardoz, Spain, Victoria Gonzalo, Javier Montero, Burgos, Spain, Alejandro Sousa-Escandon, Juan Leon, Monforte de Lemos, Spain, Jose Luis Pontones, Francisco Delgado, Valencia, Spain, Miguel Adriazola, Angela Pascual, Palencia, Spain, Jesus Calleja, Ana Ruano, Valladolid, Spain, Luis Martinez-Piñeiro, Javier Angulo-Cuesta, Madrid, Spain

Introduction: Intravesical Hyperthermia with  Mitomycin-C (MMC) is used in intermediate risk (IR) Non muscle invasive bladder cancer (NMIBC) and also in High risk (HRk) NMIBC due to the BCG shortage. 

The aim is to analyze real-world data on the long-term outcomes of adjuvant Hyperthermic IntraVEsical Chemotherapy (HIVEC) with MMC and COMBAT® Bladder Recirculation System (BRS) for patients with NMIBC.

Methods: Prospective observational trial including patients with NMIBC treated with HIVEC using Combat BRS in 9 academic institutions in Spain between 2012-2020.
Treatment modalities included in this study were based on weekly induction HIVEC MMC, either alone or followed by monthly maintenance. Number of instillations was variable according to the criteria of the different centres involved, patient risk group and treatment tolerability. All patients gave informed consent.

We defined Safety population (SAF) as those with at least one instillation. They were evaluated according to the number and severity of adverse events (AEs).
We defined Full Analysis Set population (FAS) as those treated with HIVEC- MMC 40 mg in the adjuvant setting after transurethral resection of the bladder, together with baseline data and clinical follow-up. In this population Treatment outcomes (recurrence, progression, overall survival) were evaluated, including only those patients of whom information about cancer risk status and follow-up was available.

Clinical follow-up of the cohort was updated in June 2021.

Results: SAF population included 592 patients, of whom 406 (68.6%) did not present AEs and 186 (31.4%) suffered at least one AE: 170 (20.7%) were grade 1-2 and 16 (2.7%) grade 3-4. The most frequent AEs were dysuria (10%), pain (7.1%), urgency (5.7%), rash (4.9%), bladder spasms (3.7%) and haematuria (3.6%).
FAS population included 502 patients who received a median number of 8.8 ± 3.3 (range 1-20) instillations. Median follow-up was 24.5 ± 16.5 (range 1-81) months.

According to EAU 2020 risk groups, 297 (59.2%) patients were intermediate risk (IR) and 205 (40.8%) were high risk (HRk). Five-year recurrence and progression-free survival rates were 50.4% (53.3% for IR and 47.1% for HRk) and 89.8% (94.0% for IR and 84.2% for HRk), respectively.

Multivariate analysis showed that recurrent tumours (hazard ratio -HR- 1.83), duration of HIVEC therapy < 4 months (HR 1.72) and HaRk group (HR 1.47) were identied as risk factors for recurrence. On the other hand,  independent factors for progression were HRk (HR 3.89), recurrent tumours (HR 3.32) and no maintenance therapy (HR 2.37). Factors influencing overall survival were patient age at diagnosis (HR 3.36) and treatment duration (HR 1.82).

Conclusions: HIVEC using BRS is effective, safe and well tolerated. Longer treatment duration, non-recurrent patients and intermediate risk disease are predictors of response. Monthly adjuvant HIVEC-MMC maintenance decreases the progression rate of NMIBC.

Source of Funding: None